Cataracts, defined as opacification of the lens, are multifactorial in origin. Epidemiological studies have identified increasing age, female gender, exposure to non-ionizing or ionizing radiation, metabolic disorders (such as diabetes mellitus), drugs (such as corticosteroids and anticancer agents) as risk factors. Cataracts have been reproduced in animal experiments that have confirmed the association of these factors as cataractogenic and identified the mechanisms of action. Among the animal models of human cataract disease, the administration of
N-methyl-
N-nitrosourea (MNU), an alkylating agent, to rats damages the DNA of lens epithelial cells, leading to apoptosis and ultimately lens opacity. The sensitivity of lens epithelial cells to MNU is inversely related to the age of the animals. When 70 mg/kg MNU was administered intraperitoneally to 15-day-old rats, in 4 weeks time, nuclear as well as cortical cataracts developed; no mortality and no gender differences were seen. Since the MNU-induced 15-day-old rat model develops cataract rapidly and consistently, it may be useful in screening anticataractogenic agents.
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